The role mammalian ribonucleotide reductase plays in regulating DNA synthesis and cell proliferation will be investigated, especially the relationship to neoplastic transformation and events concomitant with the initiation of cell division. The mechanisms by which large increases in ribonucleotide reductase activity is achieved on transformation of a cell from a dormant state to one of active cell replication will be studied. In addition the significance of the apparent association of several DNA synthetic enzymes with a membrane organelle will be determined. Further purification of Novikoff tumor ribonucleotide reductase will be pursued. A consequence of this would be the determination of whether or not vitamin B12 is an integral part of this enzyme complex. The utilization of the mammalian ribonucleotide reductase reaction for screening potential chemotherapeutic drugs directed against this reaction is a corollary of this research.